Molecular hydrogen reduces acute exercise-induced inflammatory and oxidative stress status

Free Radic Biol Med. 2018 Dec;129:186-193. doi: 10.1016/j.freeradbiomed.2018.09.028. Epub 2018 Sep 19.


Physical exercise induces inflammatory and oxidative markers production in the skeletal muscle and this process is under the control of both endogenous and exogenous modulators. Recently, molecular hydrogen (H2) has been described as a therapeutic gas able to reduced oxidative stress in a number of conditions. However, nothing is known about its putative role in the inflammatory and oxidative status during a session of acute physical exercise in sedentary rats. Therefore, we tested the hypothesis that H2 attenuates both inflammation and oxidative stress induced by acute physical exercise. Rats ran at 80% of their maximum running velocity on a closed treadmill inhaling either the H2 gas (2% H2, 21% O2, balanced with N2) or the control gas (0% H2, 21% O2, balanced with N2) and were euthanized immediately or 3 h after exercise. We assessed plasma levels of inflammatory cytokines [tumor necrosis factor-α (TNF-α), interleukin (IL)-1β and IL-6] and oxidative markers [superoxide dismutase (SOD), thiobarbituric acid reactive species (TBARS) and nitrite/nitrate (NOx)]. In addition, we evaluated the phosphorylation status of intracellular signaling proteins [glycogen synthase kinase type 3 (GSK3α/β) and the cAMP responsive element binding protein (CREB)] that modulate several processes in the skeletal muscle during exercise, including changes in exercise-induced reactive oxygen species (ROS) production. As expected, physical exercise increased virtually all the analyzed parameters. In the running rats, H2 blunted exercise-induced plasma inflammatory cytokines (TNF-α and IL-6) surges. Regarding the oxidative stress markers, H2 caused further increases in exercise-induced SOD activity and attenuated the exercise-induced increases in TBARS 3 h after exercise. Moreover, GSK3α/β phosphorylation was not affected by exercise or H2 inhalation. Otherwise, exercise caused an increased CREB phosphorylation which was attenuated by H2. These data are consistent with the notion that H2 plays a key role in decreasing exercise-induced inflammation, oxidative stress, and cellular stress.

Keywords: Cytokines; Inflammation; Muscle; ROS.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Inhalation
  • Animals
  • Anti-Inflammatory Agents / pharmacology*
  • Antioxidants / pharmacology*
  • Cyclic AMP Response Element-Binding Protein / blood
  • Cyclic AMP Response Element-Binding Protein / genetics
  • Glycogen Synthase Kinase 3 beta / blood
  • Glycogen Synthase Kinase 3 beta / genetics
  • Hydrogen / pharmacology*
  • Interleukin-1beta / antagonists & inhibitors
  • Interleukin-1beta / blood
  • Interleukin-1beta / genetics
  • Interleukin-6 / antagonists & inhibitors
  • Interleukin-6 / blood
  • Interleukin-6 / genetics
  • Isoenzymes / blood
  • Isoenzymes / genetics
  • Male
  • Muscle, Skeletal / drug effects*
  • Muscle, Skeletal / metabolism
  • Muscle, Skeletal / physiopathology
  • Nitrates / antagonists & inhibitors
  • Nitrates / blood
  • Nitrites / antagonists & inhibitors
  • Nitrites / blood
  • Oxidative Stress / drug effects*
  • Physical Conditioning, Animal / methods
  • Physical Exertion / drug effects
  • Rats
  • Rats, Wistar
  • Reactive Oxygen Species / antagonists & inhibitors*
  • Reactive Oxygen Species / blood
  • Running
  • Superoxide Dismutase / blood
  • Superoxide Dismutase / genetics
  • Thiobarbituric Acid Reactive Substances / metabolism
  • Tumor Necrosis Factor-alpha / antagonists & inhibitors
  • Tumor Necrosis Factor-alpha / blood
  • Tumor Necrosis Factor-alpha / genetics


  • Anti-Inflammatory Agents
  • Antioxidants
  • CREB1 protein, rat
  • Cyclic AMP Response Element-Binding Protein
  • IL1B protein, rat
  • Il6 protein, rat
  • Interleukin-1beta
  • Interleukin-6
  • Isoenzymes
  • Nitrates
  • Nitrites
  • Reactive Oxygen Species
  • Thiobarbituric Acid Reactive Substances
  • Tumor Necrosis Factor-alpha
  • Hydrogen
  • Superoxide Dismutase
  • Glycogen Synthase Kinase 3 beta
  • Gsk3b protein, rat